title: N-terminal domain of the androgen receptor contains a region that can promote cytoplasmic localization.
abstract: Nucleocytoplasmic trafficking of the androgen receptor (AR) represents an essential step in androgen action. To determine whether the amino-terminal domain (NTD) contains potential nuclear import and/or export signals, deletion mutants of the NTD tagged with green fluorescent protein (GFP) were generated and tested for their intracellular localization in both AR-negative and AR-positive cell lines. Subcellular localization analysis suggested a role of the NTD in regulating AR subcellular localization and revealed that the region of a.a. 50-250 of the NTD of AR (AR(50-250)) could promote cytoplasmic localization. Leptomycin B inhibited the activity of AR(50-250), suggesting that AR(50-250) export is mediated through exportin 1, either directly or indirectly. These observations argue for an important role of the NTD in regulating AR nucleocytoplasmic trafficking and will facilitate further investigation of interactions among different signals in regulating AR nucleocytoplasmic trafficking, which may lead to new approaches to inhibit AR nuclear localization.
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Javid A
authors.initials: JA
authors.lastname: Dar
authors.forename: Kurtis
authors.initials: K
authors.lastname: Eisermann
authors.forename: Khalid Z
authors.initials: KZ
authors.lastname: Masoodi
authors.forename: Junkui
authors.initials: J
authors.lastname: Ai
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Tyler
authors.initials: T
authors.lastname: Severance
authors.forename: Sharanya D
authors.initials: SD
authors.lastname: Sampath-Kumar
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wang
mesh_terms: D021581:Active Transport, Cell Nucleus; D059002:Androgen Receptor Antagonists / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D010449:Peptide Mapping; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D059002:Androgen Receptor Antagonists; D000728:Androgens; D005231:Fatty Acids, Unsaturated; D021382:Protein Sorting Signals; D011944:Receptors, Androgen; D011993:Recombinant Fusion Proteins; D013196:Dihydrotestosterone; D049452:Green Fluorescent Proteins; C038753:leptomycin B
keywords: AR(50–250); Androgen receptor; Leptomycin B; NTD; Subcellular localization